This program-project has two interdependent themes. To use molecular biology and genetics both to elucidate the life cycles of human tumor viruses and to characterize the mechanisms by which these tumor viruses transform infected cells. Lambert studies papillomaviruses; Loeb studies hepatitis B viruses; Mertz studies papova and hepatitis B viruses; Panganiban studies retroviruses; and Sugden studies human herpesviruses. These investigators use parallel approaches to study most known human tumor viruses. Their shared intellectual and experimental commitments support advances in one family of tumor viruses being applied to another. Loeb and Panganiban work on viruses-duck, heron, and human hepatitis B viruses and human immunodeficiency virus, which use reverse transcription in their life cycles. They are characterizing the synthesis of the viral genomes, genome structure, and virion maturations. Mertz works on the mechanism of export from the nucleus of viral RNAs, a problem of clear interest to Panganiban. Mertz also is defining one means by which cellular proteins regulate simian virus 40 late gene expression, a wide-ranging problem of interest central both to Lambert and Sugden. Lambert is defining the mechanisms by which human papilloma viral oncogenes affect host cell physiology. He is also dissecting the mechanisms by which human papilloma viral oncogenes affect host cell physiology. He is also dissecting the regulation and replication of papillomaviral plasmids in parallel with Sugden's research on the replication of Epstein-Barr viral plasmids. Sugden studies too an Epstein-Barr viral oncogene in order to reveal its effects on host cell physiology. All of this research has as its goal understanding viral carcinogenesis both by tractable viruses and by the viruses that cause cancer in people. All of these studies will provide new understandings of how tumor viruses propagate and act as carcinogens.